Objective: To explore the effect of different obesity indicators in predicting cardiovascular and cerebrovascular diseases (CVD) risk among patients with type 2 diabetes mellitus (T2DM), so as to provide the evidence for the early identification of CVD risk among T2DM patients. Methods: The patients with T2DM under community management in Qingpu District, Shanghai Municipality were selected as the study subjects in January 2025. Basic information such as gender, age, and blood glucose control status were collected through the Shanghai Chronic Disease Information Management System, while history of CVD were obtained from residents' electronic health records and the Shanghai Disease Control Information Platform. Obesity was assessed using body mass index (BMI), waist circumference (WC), BMI combined with WC, waist-to-height ratio (WHtR), and triglyceride (TG) combined with WC indicators. The association between obesity and CVD was analyzed using multivariable logistic regression models. The predictive effect of each obesity indicators for CVD was evaluated using the area under the receiver operating characteristic curve (AUC). Results: A total of 4 367 patients with T2DM were included, including 2 121 males (48.57%) and 2 246 females (51.43%). The average age was (68.71±8.05) years. The prevalence of CVD was 44.49%. Multivariable logistic regression analysis showed that after adjusting for age, education level, history of hypertension, duration of T2DM, use of glucose-lowering medications, renal function, and blood glucose control status, obese T2DM patients had a 389.4% increased risk of CVD compared to those with normal BMI; centrally obese T2DM patients had a 100.4% increased risk compared to those with normal WC; T2DM patients with isolated general obesity and compound obesity had 161.0% and 241.1% increased risks of CVD, respectively, compared to those with normal BMI and WC; centrally obese T2DM patients had a 100.4% increased risk compared to those with normal WHtR; T2DM patients with normal TG-high WC and high TG-high WC phenotypes had 83.1% and 68.8% increased risks of CVD, respectively, compared to those with normal TG and normal WC (all P<0.05). BMI had the highest AUC, at 0.714, with sensitivity and specificity of 0.675 and 0.642, respectively. This was followed by BMI combined with WC, which had an AUC of 0.707, with sensitivity and specificity of 0.635 and 0.679, respectively. Conclusions Obesity defined by BMI, WC, BMI combined with WC, WHtR, and TG combined with WC increases the risk of CVD among patients with T2DM. BMI and BMI combined with WC have better predictive effect in predicting CVD risk among patients with T2DM, and can be used as the primary obesity indicators for CVD risk screening.

To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective:To investigate the effects of multimodal and multisensory stimulation training on feeding-swallowing and neurological functions in stroke patients with dysphagia.Methods:Stroke patients with dysphagia treated at Henan Provincial People's Hospital from January 2023 to October 2024 were enrolled. Patients were randomly divided into three groups according to the random number table method, with 36 patients in each group. These three groups underwent different interventions for a period of 8 weeks: multisensory stimulation intervention (stimulation group), multimodal rehabilitation training intervention (rehabilitation group), and innovative multimodal and multisensory stimulation training intervention (combined group). The Kubota water swallow test and functional oral intake scale (FOIS) were used to assess the effective improvement rate of feeding function. Differences in scores of modified Mann assessment of swallowing (MMASA), swallowing quality of life (SWAL-QOL), and National Institute of Health Stroke scale (NIHSS) among the three groups were compared before intervention, and at 4 and 8 weeks post-intervention. SPSS 27.0 software was used to analyze the data by one-way ANOVA, repeated measures ANOVA, Kruskal-Wallis H test, Mann-Whitney U test and Pearson correlation analysis. Results:(1) After 8 weeks of intervention, the effective improvement rates of feeding function were 75.00%(27/36) and 72.22%(26/36) in the stimulation group and rehabilitation group, respectively, which were both lower than that in the combined group (94.44%(34/36), both P<0.05). (2) The interaction effect between time and group was significant in MMASA scores among the three groups before and after intervention ( F=2.569, P<0.05). MMASA scores at 8 weeks post-intervention were higher than those at 4 weeks post-intervention and baseline in all groups (all P<0.05), and scores at 4 weeks post-intervention were also higher than those at baseline (all P<0.05). At 4 and 8 weeks post-intervention, MMASA scores in the combined group (85.64±11.26, 92.56±10.55) were higher than those in the stimulation group (73.52±12.65, 82.97±12.84) and rehabilitation group (72.47±11.38, 84.39±12.29) (all P<0.05). (3) The interaction effect between time and group was significant in SWAL-QOL total scores among the three groups before and after intervention ( F=18.561, P<0.05). SWAL-QOL total scores at 8 weeks post-intervention were higher than those at 4 weeks post-intervention and baseline in all groups ( P<0.05), and scores at 4 weeks post-intervention were also higher than those at baseline (all P<0.05). At 4 and 8 weeks post-intervention, SWAL-QOL total scores in the combined group (115.64±9.26, 135.68±9.55) were higher than those in the stimulation group (108.42±8.65, 113.75±8.84) and rehabilitation group (108.37±8.38, 114.39±9.29) (all P<0.05). (4) The interaction effect between time and group was significant in NIHSS scores among the three groups before and after intervention ( F=7.890, P<0.05). NIHSS scores at 8 weeks post-intervention were lower than those at 4 weeks post-intervention and baseline in all groups (all P<0.05), and scores at 4 weeks post-intervention were also lower than those at baseline (all P<0.05). At 4 and 8 weeks post-intervention, NIHSS scores in the combined group (8.36±1.35, 5.22±1.05) were lower than those in the stimulation group (11.65±2.11, 8.78±1.12) and rehabilitation group (11.32±2.03, 8.36±1.17) (all P<0.05). Conclusion:Multimodal and multisensory stimulation training can improve feeding-swallowing function and neurological impairment in stroke patients with dysphagia, with intervention effects superior to those of either approach used alone.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Aim To investigate the protective effect of Siwu decoction(SWD)on immune injury induced by 60Coγ-rays in mice and the related mechanism.Meth-ods C57BL/6J mice were randomly divided into six groups:Control group(Control),Model group(Mod-el),Siwu decoction low-dose group(SWD-L),Siwu decoction medium-dose group(SWD-M),Siwu decoc-tion high-dose group(SWD-H)and resveratrol positive group(Resveratrol,Res).The drug was continued to be administered 11 days before and after irradiation,with a single whole-body irradiation of 4 Gy,and all in-dexes were detected three days after irradiation.The changes of peripheral blood and organ indexes were de-tected.Serum levels of cytokine interferon gamma(IFN-γ),interleukin-1 β(IL-1 β),IL-2,IL-4,IL-6,IL-10,IL-17,transforming growth factor-β(TGF-β),tumor necrosis factor(TNF)-α,and immunoglobulin A(IgA),IgG,IgM,and complement protein 3(C3),C4 content were detected by enzyme-linked immunosorbent assay(ELISA).B lymphocytes,T lymphocytes,NK cells in spleen and T lymphocytes in thymus were de-tected by flow cytometry.The pathological changes of spleen and thymus were analyzed by hematoxylin-eosin(HE)staining.The expression of Sirt 1 protein in spleen after radiation was detected by immunofluores-cence staining.The protein contents of Sirt1,PI3K,Akt,p-Akt and mTOR in spleen were detected by Western blot assay.Results SWD could significantly increase LYMPH％and reduce pathological injury of spleen and thymus.Flow cytometry showed that SWD could significantly increase the percentage of CD19+B lymphocytes in spleen,decrease the percentage of NK lymphocytes and the ratio of CD4+/CD8+in spleen and thymus.ELISA results showed that SWD signifi-cantly inhibited the expression of IL-1 β,IL-2,IL-6,IL-17,IFN-γ,TGF-β,TNF-α,and increased the content of anti-inflammatory factors IL-4 and IL-10.At the same time,SWD significantly inhibited the increase of IgA,IgG,IgM,C3 and C4 induced by radiation.The results of immunofluorescence staining and Western blot showed that SWD could decrease the expression of PI3K,Akt,p-Akt and mTOR protein,and enhance the expression of Sirt1 protein.Conclusions SWD has obvious preventive effect on immune damage induced by 60Co gamma radiation in mice.The mechanism may be related to Sirt1-PI3K-Akt-mTOR.

Radical resection of mid-and low-rectal cancer requires not only oncologic safety but also preservation of organs and postoperative bowel function.While a 1-2 cm distal resection margin has been largely accepted,the optimal length of the proximal margin remains highly controversial.Clinically,the"10-cm rule"derived from colon cancer is often referenced,yet its applicability to rectal cancer lacks consistent supporting evidence.Previous studies have shown that an excessively long proximal margin may increase anastomotic tension and lead to anastomotic leakage,whereas insufficient resection heightens the risk of positive margins and local recurrence.In addition,the extent of lymph node metastasis,vascular perfusion of the proximal bowel,radiation-induced injury after neoadjuvant chemoradiotherapy,and postoperative bowel function-particularly low anterior resection syndrome-are all important factors influencing the selection of the proximal margin.In recent years,the application of indocyanine green fluorescence imaging has provided new evidence for intraoperative assessment of bowel perfusion;for patients receiving neoadjuvant chemoradiotherapy,radiation injury presents a gradient pattern,and resecting approximately≥20 cm proximal to the tumor may reduce the incidence of anastomosis-related complications.Based on current literature,this review provides a systematic overview of the historical evolution,influencing factors,and clinical evidence regarding proximal resection margins in rectal cancer surgery,with the aim of informing individualized margin selection and optimizing surgical strategies.

Objective:To investigate the effects of multimodal and multisensory stimulation training on feeding-swallowing and neurological functions in stroke patients with dysphagia.Methods:Stroke patients with dysphagia treated at Henan Provincial People's Hospital from January 2023 to October 2024 were enrolled. Patients were randomly divided into three groups according to the random number table method, with 36 patients in each group. These three groups underwent different interventions for a period of 8 weeks: multisensory stimulation intervention (stimulation group), multimodal rehabilitation training intervention (rehabilitation group), and innovative multimodal and multisensory stimulation training intervention (combined group). The Kubota water swallow test and functional oral intake scale (FOIS) were used to assess the effective improvement rate of feeding function. Differences in scores of modified Mann assessment of swallowing (MMASA), swallowing quality of life (SWAL-QOL), and National Institute of Health Stroke scale (NIHSS) among the three groups were compared before intervention, and at 4 and 8 weeks post-intervention. SPSS 27.0 software was used to analyze the data by one-way ANOVA, repeated measures ANOVA, Kruskal-Wallis H test, Mann-Whitney U test and Pearson correlation analysis. Results:(1) After 8 weeks of intervention, the effective improvement rates of feeding function were 75.00%(27/36) and 72.22%(26/36) in the stimulation group and rehabilitation group, respectively, which were both lower than that in the combined group (94.44%(34/36), both P<0.05). (2) The interaction effect between time and group was significant in MMASA scores among the three groups before and after intervention ( F=2.569, P<0.05). MMASA scores at 8 weeks post-intervention were higher than those at 4 weeks post-intervention and baseline in all groups (all P<0.05), and scores at 4 weeks post-intervention were also higher than those at baseline (all P<0.05). At 4 and 8 weeks post-intervention, MMASA scores in the combined group (85.64±11.26, 92.56±10.55) were higher than those in the stimulation group (73.52±12.65, 82.97±12.84) and rehabilitation group (72.47±11.38, 84.39±12.29) (all P<0.05). (3) The interaction effect between time and group was significant in SWAL-QOL total scores among the three groups before and after intervention ( F=18.561, P<0.05). SWAL-QOL total scores at 8 weeks post-intervention were higher than those at 4 weeks post-intervention and baseline in all groups ( P<0.05), and scores at 4 weeks post-intervention were also higher than those at baseline (all P<0.05). At 4 and 8 weeks post-intervention, SWAL-QOL total scores in the combined group (115.64±9.26, 135.68±9.55) were higher than those in the stimulation group (108.42±8.65, 113.75±8.84) and rehabilitation group (108.37±8.38, 114.39±9.29) (all P<0.05). (4) The interaction effect between time and group was significant in NIHSS scores among the three groups before and after intervention ( F=7.890, P<0.05). NIHSS scores at 8 weeks post-intervention were lower than those at 4 weeks post-intervention and baseline in all groups (all P<0.05), and scores at 4 weeks post-intervention were also lower than those at baseline (all P<0.05). At 4 and 8 weeks post-intervention, NIHSS scores in the combined group (8.36±1.35, 5.22±1.05) were lower than those in the stimulation group (11.65±2.11, 8.78±1.12) and rehabilitation group (11.32±2.03, 8.36±1.17) (all P<0.05). Conclusion:Multimodal and multisensory stimulation training can improve feeding-swallowing function and neurological impairment in stroke patients with dysphagia, with intervention effects superior to those of either approach used alone.

Due to advances in treatment methods, the survival rate and quality of life of cancer patients have been improved. Radiation-induced vascular injury (RIVI) is a common adverse reaction following radiotherapy, mainly manifested as capillary injury and atherosclerosis in the irradiated area. Radiotherapy induces RIVI in the cerebral vessels, carotid arteries, coronary arteries, and large arteries through mechanisms such as endothelial cell injury and senescence, oxidative stress and inflammatory responses, angiogenesis, and vascular remodeling. In this review research progress in the pathological features, pathophysiological mechanisms, clinical manifestations, prevention and treatment strategies of RIVI was summarized, aiming to provide insights for future research on RIVI.

Objective:To explore the correlation between abnormal vital signs (e.g., heart rate, oxygen saturation, and body temperature) and acute exacerbations in patients with chronic obstructive pulmonary disease (COPD), as well as to evaluate the clinical value of continuous monitoring via wearable devices for the early warning and intervention.Methods:A multicenter cross-sectional study enrolled 335 patients with stable chronic obstructive pulmonary disease (COPD) from 12 community health centers in Beijing and Chengdu between June 2023 and May 2024. General demographic and clinical data were collected, and each participant underwent continuous monitoring of resting heart rate, oxygen saturation, and body temperature using wearable devices for 21 days. Based on whether participants had experienced acute exacerbations requiring outpatient, emergency, or inpatient treatment within the previous year, they were categorized into the acute exacerbation group and the non-exacerbation group. Differences in physiological parameters between the acute exacerbation group and non-exacerbation group were analyzed, and contributing factors were assessed using logistic regression analysis.Results:A total of 335 patients with stable COPD were enrolled, including 252 cases (75.22%) in the acute exacerbation group and 83 cases (24.78%) in the non-acute exacerbation group. There were no statistically significant differences in age, sex distribution, comorbidities, or baseline lung function between the two groups (all P>0.05). Compared with the non-acute exacerbation group, patients in the acute exacerbation group had a faster resting heart rate((76.01 ± 7.78) beats/min vs. (72.72 ± 7.35) beats/min, t=3.126, P=0.002), a higher proportion of patients with decreased oxygen saturation (1.75% (0.97%, 3.03%) vs. 0.86% (0.44%, 1.65%), Z=11.086, P=0.001), and a higher proportion of patients with elevated body temperature (0.60% (0.39%, 1.03%) vs. 0.31% (0.17%, 0.54%), Z=7.314, P=0.007). Logistic regression analysis showed that advanced age ( OR=1.051, 95% CI: 1.023-1.080), increased heart rate ( OR=1.055, 95% CI:1.013-1.098), decreased oxygen saturation ( OR=1.197, 95% CI:1.023-1.400), and elevated body temperature ( OR=1.777, 95% CI:1.148-2.752) were positively associated factors for acute exacerbation of COPD. Conclusions:Abnormalities in physiological indicators such as heart rate, oxygen saturation, and body temperature are associated with acute exacerbations in COPD patients. Continuous monitoring using wearable devices may provide a new method for early warning and timely intervention in COPD exacerbations.